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Pre‐analytical and clinical validation on the highway to implementation of novel dementia blood tests
Author(s) -
Teunissen Charlotte E.
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.050709
Subject(s) - dementia , biomarker , clinical practice , medicine , cohort , disease , population , prospective cohort study , pathology , oncology , medical physics , intensive care medicine , physical therapy , biochemistry , chemistry , environmental health
Background Blood based biomarkers for Alzheimer’s disease and other dementias are now a reality. Results in large well‐defined research cohorts suggest high potential for implementation for diagnosis (pTau, amyloid isoforms, GFAP), prognosis (pTau, GFAP, NfL) or monitoring (pTau, NfL) in clinical practice and treatment development. Implementation of novel blood based biomarkers requires several aspects to be addressed, among which pre‐analytical sample handling, patient heterogeneity and the development of cut‐offs and computer‐assisted tools for interpretation. Method To mimic pre‐analytical variations occurring in current practice, systematic experiments were performed and effects on plasma Amyloid beta(42/40), (p)Tau, NfL and GFAP levels were measured using different technologies. To understand patient heterogeneity, these markers are measured in several cohorts of normal aging elderly using Simoa technology. To develop cut‐offs and tools for interpretation, these markers are measured in a retrospective cohort of patients with various dementias. Lastly, prospective analysis of these markers in the memory clinic setting has been started. Result The generated knowledge on the most important pre‐analytical factors affecting Amyloidbeta(42/40), (p)Tau, NfL and GFAP levels resulted in the construction of a standardized operating procedure for use in clinical practise and research (Figure). Results in the normal aging population followed longitudinally show that these biomarkers are higher in patients that are proven to be amyloid positive 10 year later. Detailed results of patient biomarker heterogeneity will be presented as well as a decision tool for use in clinical practice. Lastly, pilot data on experience with these novel blood based biomarkers and the decision tools for dementia diagnosis in the memory clinic setting will be presented. Conclusion Together, the addressed are important steps towards smooth and widespread implementation of blood based biomarkers in clinical practise.